Variant chr12-32796308-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001005242.3(PKP2):c.2168-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,271,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PKP2
NM_001005242.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001853

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.229

Variant links:

Genes affected

PKP2 (HGNC:9024): (plakophilin 2) This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This gene may regulate the signaling activity of beta-catenin and is required to maintain transcription of genes that control intracellular calcium cycling including ryanodine receptor 2, ankyrin-B, triadin, and calcium channel, voltage-dependent, L type, alpha 1C. Mutations in this gene are associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy, Brugada Syndrome, and Idiopathic Ventricular Fibrillation. A processed pseudogene with high similarity to this gene has been mapped to chromosome 12p13. [provided by RefSeq, May 2022]

PKP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 12-32796308-G-A is Benign according to our data. Variant chr12-32796308-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 464424.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000126 (160/1271954) while in subpopulation AMR AF= 0.000919 (34/36992). AF 95% confidence interval is 0.000676. There are 0 homozygotes in gnomad4_exome. There are 79 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP2	NM_001005242.3 linkuse as main transcript	c.2168-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000340811.9	NP_001005242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP2	ENST00000340811.9 linkuse as main transcript	c.2168-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001005242.3	ENSP00000342800	P1	Q99959-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143384

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000453

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000458

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

160

AN:

1271954

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

633982

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.000919

Gnomad4 ASJ exome

AF:

0.000224

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.0000741

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000558

AC:

AN:

143384

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69528

show subpopulations

Gnomad4 AFR

AF:

0.0000257

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000453

Gnomad4 NFE

AF:

0.0000458

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000874

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.5

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over